Rizatriptan: A New Milestone in Migraine Treatment. Introduction ∗

Despite the important impact of migraine on the quality of life of sufferers, this extremely frequent neurological condition is being underdiagnosed and, consequently, undertreated. A recent epidemiological survey, conducted by Lipton and Stewart (1), indicates that 32% of migraineurs never consulted a physician, while 21% of them lapsed from care. Thus, only 47% of the total population of patients is currently receiving some kind of treatment.

Due to the personal and economic significance of migraine, there is a permanent interest in the development of new treatments for this debilitating disorder. New and effective therapeutic options have recently become available for controlling migraine attacks. The most promising is the triptan family of compounds which act as selective agonists of serotonin (5-HT) receptors, specifically of the 5-HT_1B/1D subtypes. A few years ago, researchers at Merck Sharp and Dohme established a strategy for designing a new triptan that should have a more rapid absorption and a higher bioavailability than sumatriptan, the compound that was initially developed in the series. These two characteristics were selected because they could translate clinically into a faster onset of pain relief and an improved consistency in the efficacy of the treatment, the most important goals for the patients that suffer from migraine attacks.

The studies presented during this symposium summarize the experience accumulated so far with the outcome of those investigations, the novel 5-HT_1B/1D agonist, rizatriptan. They confirm that the compound has very good clinical and safety profiles, and offers important advantages over other triptans that are currently being used for treating migraine attacks.

In the first contribution to the meeting, Dr Richard Hargreaves discusses the pathophysiology of migraine as well as the pharmacological properties of rizatriptan and its mode of action on the vascular and neural mechanisms that trigger and maintain the pain.

Professor Peter Goadsby subsequently discusses the efficacy of rizatriptan, including new data obtained from its direct comparison with sumatriptan, naratriptan and zolmitriptan. Clinical trials with rizatriptan have assessed a wide range of endpoints ranging from headache relief to pain free, effects on associated symptoms, return to normal function, consistency of drug efficacy and headache recurrence. These investigations have confirmed the superiority of rizatriptan over placebo, its rapid onset of action and its effectiveness in eliminating the pain at 2 h in a high percentage of patients. Moreover, rizatriptan 10-mg has been shown to be superior to sumatriptan 100 mg, naratriptan 2.5 mg and zolmitriptan 2.5 mg in terms of the percentage of patients who become pain free and of those that can function normally 2 h after treatment.

Finally, Professor Fumihiko Sakai discusses the extensive preclinical and clinical data that indicate the very good safety and tolerability profile of rizatriptan.

The information presented at the Symposium confirms that the addition of rizatriptan to clinical practice should be useful both to doctors and patients. Moreover, the data obtained from comparative clinical trials will help physicians to decide the most appropriate treatment for the individual patient.